Neoplasms

Blood and Lymph Conditions

All Conditions

Hematologic Neoplasms

Hematologic Diseases

Antineoplastic Agents

All Drugs and Chemicals

Treosulfan

Busulfan

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Treosulfan: 10 g/m² i.v. on 3 consecutive days (day -6 to -4)

Treosulfan:12 g/m² i.v. on 3 consecutive days (day -6 to -4)

Treosulfan: 14 g/m² i.v. on 3 consecutive days (day -6 to -4)

Mathias Freund, MD

Evaluation of the safety and efficacy of 3 x 10, 3 x 12 or 3 x 14 g/m² Treosulfan resp., combined with 5 x 30 mg/m² fludarabine prior to allogeneic, hematopoietic stem cell transplantation of patients with hematological malignancies, but non-eligible to standard conditioning treatment.

Dose-range Finding Treosulfan-based Conditioning

Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Advanced Hematological Malignancies After Treosulfan-based Conditioning Therapy - A Clinical Phase II Study

medac GmbH

Joachim Baumgart, PhD

Immune System Diseases

Behaviors and Mental Disorders

Nervous System Diseases

Rare Diseases

Lymphoma

Aggression

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Dementia

Aberrant Motor Behavior in Dementia

Behavioral Symptoms

Lymphosarcoma

Anti-Infective Agents

Etoposide

Cytarabine

Bendamustine Hydrochloride

Melphalan

Etoposide phosphate

Bendamustine 200 mg/m2 starting dose on day -7 and -6 Etoposide 200 mg/m2 from day -5 to day -2 Ara-C 400 mg/m2 from day -5 to day -2 Melphalan 140 mg/m2 on day -1

Bendamustine-EAM

Mª Dolores Caballero, MD

Alejandro Martín, MD

Javier Briones, MD

Juan Manuel Sancho, MD

Cristina Barrenetxea, MD

Javier López, MD

Mª José Rodríguez, MD

Jorge Gayoso, MD

Miguel Ángel Canales, MD

Carlos Grande, MD

Isidro Jarque, MD

José Rifón, MD

Andres Sánchez, MD

Cristina Castilla, MD

José Luis Bello, MD

Armando López, MD

Eulogio Conde, MD

Reyes Arranz, MD

Encarnación Monzó, MD

Rosario Varela, MD

Mª José Ramírez, MD

Fátima de la Cruz, MD

Ana Pilar González, MD

Luis Palomera, MD

Raquel del Campo, MD

Mª José Terol, MD

The purpose of this study is to determine whether Bendamustine in combination with Etoposide, Cytarabine and Melphalan (BeEAM) are effective as conditioning followed by ASCT in patients with aggressive lymphoma.

BCNU (carmustine is a nitrosurea alkylating agent used for many years in the conditioning of patients with lymphoma however this drug is hardly available in some countries in Europe, moreover to improve conditioning regimens in autologous stem cell transplant is important because the anti-tumoral effect of high dose therapy are responsible for this procedure efficacy. Although for many years few advances have been achieved in this area now new drugs can be tested in these patients.

Bendamustine is a unique cytotoxic agent with structural similarities to alkylating agents and antimetabolites, but which is non-cross-resistant with alkylating agents and other drugs in vitro and in the clinic. Early clinical studies conducted in the German Democratic Republic more than 30 years ago suggested promising activity in indolent non-Hodgkin's lymphoma (NHL). Two North American trials reported responses in more than 70% of patients with chemotherapy- and rituximab-refractory disease, suggesting that bendamustine may be the most effective drug available for this patient population. Response rates of 90% to 92%, with complete remission in 55% to 60%, have been reported in patients with follicular and mantle-cell lymphoma with the combination of bendamustine and rituximab.(Cheson 2009) Leone et all have recently reported results on the characterization of the mechanisms of action of bendamustine and its comparison with structurally related compounds as chlorambucil and phosphoramide mustard have demonstrated that bendamustine displays a distinct mechanisms of action including activation of DNA-damage stress response and apoptosis, inhibition of mitotic checkpoints, and induction of mitotic catastrophe. Also bendamustine activates a base excision DNA repair pathway rather than an alkyltransferase DNA repair mechanism.

These data suggest that bendamustine possesses mechanistic features that differentiate it from other alkylating agents and makes this old new drug an attractive one to combine with other agents in the conditioning transplant setting (Leone 2008).

Bendamustine, Cytarabine, Etoposide and Melphalan (BeEAM) as Conditioning for Autologous Stem Cell Transplant (ASCT) in Aggressive Non Hodgkin's Lymphoma (NHL).

Bendamustine, Cytarabine, Etoposide and Melphalan as Conditioning for Autologous Stem Cell Transplant in Patients With Aggressive Non Hodgkin's Lymphoma.

Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antirheumatic Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Preparation before allogeneic transplantation

Conditioning therapy

Gerhard Ehninger, MD

The primary goal of the study is to show that the treatment-related mortality of allogeneic hematopoietic stem cell transplantation an be significantly reduced by using a combination of 8 Gy total-body-irradiation and fludarabine in comparison to the conventional combination of 12 Gy TBI and 120 mg/kg Cyclophosphamide.

Transplant-related deaths because of extramedullary toxicity and graft-versus host disease remain the major causes for treatment-failure in patients with AMl receiving allogeneic hematopoietic stem cell transplantation.

In phase II study, M . Stelljes and coworkers could show, that a reduced dose of total-body- irradiation and fludarabine can be safely used in patients with AML at various disease stages. The best results could be achieved in patients who had been in complete remission by the time of inclusion.

Therefore this prospective trial was initiated to compare the new conditioning regimen with the standard regimen of 12 Gy TBI/Cyclophosphamide 120 mg/kg in patients ith AML in first remission.

After having achieved complete remission, and giving informed consent, patients are stratified according to marrow cytogenetics, age and type of induction therapy and subsequently randomized to receive on of the mentioned conditioning therapies.

The primary end-point will be non-relapse mortality. The hypothesis would be, that the one-year mortality can be reduced from 25 to 15%. Given a power of 0.8 and a first-error of 5%, 252 patients will have to be randomized.

Secondary endpoints include:

3 year overall-and disease-free survival Rate of grade II-IV acute GvHD Rate of grade 3-4 extramedullary toxicity

Standard vs. Reduced-Intensity Conditioning in Patients With Acute Myeloid Leukemia in First Remission

Randomized Phase III Comparison of 12 Gy TBI and Cyclophosphamide 120 mg/kg With Fludarabine 120 mg/Sqm and 8 Gy TBI Before Allogeneic Transplantation in Patients With Acute Myeloid Leukemia in First Remission

Proportion of patients dying without prior relapse

Proportion of patients alive without relapse

Percentage of patients with grade II-IV acute GvHD

University Hospital Carl Gustav Carus

University Hospital Dresden

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Dose-range Finding Treosulfan-based Conditioning	NCT01063647	Hematological M...	Treosulfan Treosulfan Treosulfan	18 Years -	medac GmbH
Bendamustine, Cytarabine, Etoposide and Melphalan (BeEAM) as Conditioning for Autologous Stem Cell Transplant (ASCT) in Aggressive Non Hodgkin's Lymphoma (NHL).	NCT01296256	Bendamustine Conditioning Th... Autologous Stem... Aggressive Non ...	Bendamustine-EA...	18 Years - 70 Years	Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
Standard vs. Reduced-Intensity Conditioning in Patients With Acute Myeloid Leukemia in First Remission	NCT00150878	Acute Myeloid L...	Conditioning th...	18 Years - 60 Years	University Hospital Carl Gustav Carus

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